Dimethyl Sulfoxide → (2R,4S,4aS)-11-fluoro-8-(2-(2-methoxyethylamino)pyrimidin-4-yl)-2,4-dimethyl-2,4,4a,6-tetrahydro-1H,1'H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5'-pyrimidine]-2',4',6'(3'H)-trione

HRID 245567ノート

反応式

HRID 245567 の反応式
[CH3:1][O:2][CH2:3][CH2:4][NH2:5].[F:6][C:7]1[C:8]2[O:33][N:32]=[C:31]([C:34]3[CH:39]=[CH:38][N:37]=[C:36](S(C)(=O)=O)[N:35]=3)[C:9]=2[CH:10]=[C:11]2[C:24]=1[N:23]1[CH2:25][C@@H:26]([CH3:30])[O:27][C@@H:28]([CH3:29])[C@@H:22]1[C:13]1([C:18](=[O:19])[NH:17][C:16](=[O:20])[NH:15][C:14]1=[O:21])[CH2:12]2.CS(C)=O.O(C(N)C)C>C1COCC1>[F:6][C:7]1[C:8]2[O:33][N:32]=[C:31]([C:34]3[CH:39]=[CH:38][N:37]=[C:36]([NH:5][CH2:4][CH2:3][O:2][CH3:1])[N:35]=3)[C:9]=2[CH:10]=[C:11]2[C:24]=1[N:23]1[CH2:25][C@@H:26]([CH3:30])[O:27][C@@H:28]([CH3:29])[C@@H:22]1[C:13]1([C:18](=[O:19])[NH:17][C:16](=[O:20])[NH:15][C:14]1=[O:21])[CH2:12]2

参加物

6

反応物 4

HCID 679Dimethyl SulfoxideHCID 80182-MethoxyethylamineHCID 19353429MethoxyethanamineHCID 67431840(2R,4S,4 aS)-11-fluoro-2,4-dimethyl-8-(2-(methylsulfonyl)pyrimidin-4-yl)-2,4,4a,6-tetrahydro-1H,1'H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5'-pyrimidine]-2',4',6'(3'H)-trione

生成物 1

HCID 67433042(2R,4S,4aS)-11-fluoro-8-(2-(2-methoxyethylamino)pyrimidin-4-yl)-2,4-dimethyl-2,4,4a,6-tetrahydro-1H,1'H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5'-pyrimidine]-2',4',6'(3'H)-trione収率 76.2%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

2-Methoxyethanamine (8.70 μL, 0.10 mmol) was added o a solution of (2R,4S,4aS)-11-fluoro-2,4-dimethyl-8-(2-(methylsulfonyl)pyrimidin-4-yl)-2,4,4a,6-tetrahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5′-pyrimidine]-2′,4′,6′(3H)-trione (Example 169, 50 mg, 0.09 mmol) in THF (5 mL), and the mixture was stirred at room temperature for 3 hours, DMSO (1 ml) was added followed by the addition of 2 more equivalence of methoxylethanamine, the mixture was stirred at room temperature for over night. The crude was concentrated and purified by reverse phase silica gel column chromatography (20-70% MeCN in water gradient, 0.1% TFA) to give 37 mg of product.

後処理

  1. stirringthe mixture was stirred at room temperature for over night
  2. concentrationThe crude was concentrated
  3. custompurified by reverse phase silica gel column chromatography (20-70% MeCN in water gradient, 0.1% TFA)

出典と根拠

ORDレコード
ord-2aaaae147b0c400a8fca3b08cd120347
出典データセット
uspto-grants-2014_02
特許番号
US08658641B2

反応ノート

読み込み中…